PhD Public Lecture - David Dick (AP Math)

Title: MULTI-SCALE EVOLUTION OF VIRULENCE OF HIV-1

Abstract: HIV-1 is a rapidly replicating retrovirus that faces two distinct fitness landscapes: within-host HIV-1 faces viral competition for host cells and for escape from the immune system, and between hosts HIV-1 faces a transmission bottleneck in which the majority of new infections are started by a single virus strain. Possibly as a result of these conflicting selective pressures, the rate of evolution of HIV-1 tends to be greater within-host than between hosts.  As further evidence of the conflict between transmission fitness and within-host fitness, experimental evidence demonstrates that subtypes A and D are 100-fold more fit than subtype C in in vitro fitness competitions, yet subtype C dominates the global spread of new infections. It is unclear whether this discrepancy is caused by differences in within- and between-host fitness, or primarily reflects differences in in vitro versus in vivo fitness measures.

To elucidate this conflict between within- and between-host fitness we develop a multi-scale simulation of HIV-1 transmission, analyze the results of a four year 8000 participant study in Uganda and Zimbabwe, and develop a non-linear mixed-effects model for a meta-analysis of 143 non-human primates.

We identify differences in viruses’ life history traits, in non-human primates, and offer a hypothesis for the within- and between-host differences in evolutionary rates. While some of the viruses’ life history traits are under selective pressure within-host, traits that are responsible for the efficiency of transmission to a new host are not under direct selection within-host and thus are subject to drift. Combined with the necessity of transmission through an extremely severe, competitive bottleneck, this results in the preferential transmission of founder-like viral lineages.